The overall objective of the proposed study is directed toward elucidation of the origin of human pandemic influenza viruses. Our studies showed that a "new" strain of influenza virus can be selected in vivo and cause an epidemic of disease. Turkeys possessing low levels of antibodies to the hemagglutinin of turkey influenza virus and to the neuraminidase of fowl-plague virus were mixedly infected with fowl-plague virus and turkey influenza viruses. Recombinant influenza viruses possessing the hemagglutinin of FPV and the neuraminidase antigen of turkey influenza virus became the dominant viruses present and killed the turkeys. These recombinant influenza viruses spread under natural conditions of transmission to contact turkeys and caused a miniepidemic of disease. Studies on viruses isolated in USSR indicated that recombination may occur between influenza A viruses in nature. The Asian strain of human influenza disappeared from the human population in 1968 when the Hong Kong strain appeared. Two influenza viruses isolated from ducks in Germany in 1972 possess hemagglutinin subunits immunologically and biochemically closely related to the Asian/57 influenza viruses. Studies on the immune response of human adults showed that they fail to mount an immune response to the "specific" antigenic determinant on the hemagglutinin of the recent (A/Port Chalmers/73) strain of influenza. Temperature-sensitive mutants of the highly virulent A/turkey/Ontario/ 7732/66 strain of influenza have been isolated for studies on the molecular basis of virulence.